PROJECT SUMMARY/ABSTRACT Anxiety disorders are the most common psychiatric illnesses of childhood, affecting 10-20% of youth. Childhood anxiety often has a chronic course, negatively affecting academic, social, and adaptive functioning, and increases the risk for mental illness throughout life. Research has highlighted a number of risk factors that likely contribute to the development and maintenance of anxiety. However, there is limited understanding of the earliest precursors of anxiety or how multiple risk factors interact within and across development to influence anxiety risk. Prospective studies beginning in infancy are needed to explicate the origins of anxiety so that (a) biomarkers can be discovered that identify at-risk children prior to the emergence of symptoms and (b) preventive strategies can be developed and implemented with at-risk children. The overall goal of the current project is to test the combined effects of neural, physiological, behavioral, and environmental risk factors in early life on vulnerability to childhood anxiety. The study aims will be accomplished by following an established longitudinal cohort (R01 MH078829; N=807). The current study will build on an extensive database that includes repeated assessments of neurophysiology (EEG, ERP), neural metabolic functioning (fNIRS), physiological stress reactivity, behavioral indicators of reactivity to threat, and family environmental risk (maternal psychopathology, stress exposures) between infancy and age 3 years. In the current proposal, we seek funds to support a follow up study at ages 5 and 7 years. At these ages, we will phenotype our cohort for anxiety symptomatology, as well as implement a battery of brain-based measures similar to what was used at age 3 years. Analyses will test whether early patterns of neural processing (in infancy and again at age 3 years) predict risk for later anxiety; examine how measures of neural, physiological, behavioral, and family environment factors jointly contribute to the development of anxiety; and explore whether different patterns of risk factors and trajectories of development predict different anxiety phenotypes. We expect that the findings will (a) elucidate the neurodevelopmental bases of anxiety, (b) contribute to the discovery of non-invasive biomarkers that can identify at-risk children and (c) inform the design of innovative strategies to prevent the development of anxiety.